Targeting the multifaceted neurotoxicity of Alzheimer's disease by tailored functionalisation of the curcumin scaffold.
Eur J Med Chem
; 252: 115297, 2023 Apr 05.
Article
in En
| MEDLINE
| ID: mdl-36996713
ABSTRACT
Simultaneous modulation of multifaceted toxicity arising from neuroinflammation, oxidative stress, and mitochondrial dysfunction represents a valuable therapeutic strategy to tackle Alzheimer's disease. Among the significant hallmarks of the disorder, Aß protein and its aggregation products are well-recognised triggers of the neurotoxic cascade. In this study, by tailored modification of the curcumin-based lead compound 1, we aimed at developing a small library of hybrid compounds targeting Aß protein oligomerisation and the consequent neurotoxic events. Interestingly, from in vitro studies, analogues 3 and 4, bearing a substituted triazole moiety, emerged as multifunctional agents able to counteract Aß aggregation, neuroinflammation and oxidative stress. In vivo proof-of-concept evaluations, performed in a Drosophila oxidative stress model, allowed us to identify compound 4 as a promising lead candidate.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Curcumin
/
Alzheimer Disease
Limits:
Humans
Language:
En
Journal:
Eur J Med Chem
Year:
2023
Document type:
Article
Affiliation country:
Italia